Search Results (1,154)

Background/Objectives: Cecal ligation and puncture (CLP)-induced sepsis is accompanied by intestinal tight-junction disruption, circulating markers of barrier dysfunction, oxidative stress, bacterial dissemination, and multi-organ injury. This study evaluated the protective effects of chemically characterized pomegranate peel extract (PPE) and punicalagin (PUN) in a rat CLP model. Methods: Forty-eight female Wistar rats were randomized into six groups (n = 8): Sham, CLP, CLP + PPE 150 mg/kg, CLP + PPE 300 mg/kg, CLP + PUN 50 mg/kg, and non-septic PPE 300 mg/kg. Treatments were administered orally 1 h after surgery. Animals were monitored for 48 h and sampled at a predefined humane endpoint or at 48 h. Results: CLP reduced ileal ZO-1 and occludin abundance and increased serum diamine oxidase, D-lactate, and plasma endotoxin (all omnibus p < 0.001). Relative to untreated CLP, PPE 300 mg/kg increased ZO-1 and occludin by 219% and 236%, respectively, and reduced circulating markers consistent with intestinal barrier dysfunction, oxidative stress, lactate, and multi-organ injury. PPE 300 mg/kg and PUN 50 mg/kg were also associated with higher hepatic SIRT1/PGC-1α expression, lower recoverable aerobic bacterial burden, less histological injury, and higher observed 48 h survival (7/8 and 8/8 vs. 2/8 in CLP). Conclusions: PPE and PUN produced coordinated protective changes in this experimental CLP model. These biomarker-based and survival findings support further preclinical investigation of standardized pomegranate-derived preparations as potential adjunctive interventions; they do not establish direct intestinal permeability, mitochondrial restoration, clinical therapeutic efficacy, or a punicalagin-mediated mechanism. Full article

Oral frailty is an emerging geriatric syndrome characterized by subtle and multifactorial declines in oral function that may precede clinically apparent oral dysfunction. Increasing evidence suggests that oral frailty is closely associated with physical frailty, sarcopenia, malnutrition, and other indicators of systemic vulnerability, highlighting its potential role in the early detection of functional decline. However, practical approaches to early detection and intervention remain challenging because conventional assessments of oral function often require specialized equipment and professional expertise. This review summarizes recent advances in the assessment, clinical significance, and management of oral frailty, with particular emphasis on practical screening and its implications for early intervention. We discuss the utility and limitations of questionnaire-based screening tools, including the Oral Frailty Index-8 (OFI-8) and Oral frailty five-item checklist (OF-5), which enable simple identification of individuals at increased risk in community and clinical settings. We also introduce findings from the FESTA study indicating that cystatin C-related indices, including the creatinine-to-cystatin C ratio and the eGFRcys/eGFRcre ratio, may reflect skeletal muscle mass and are associated with oral functional decline, particularly reduced tongue pressure. Comparative and longitudinal evidence further suggests an association between oral frailty and subsequent physical frailty, while OF-5 may help identify individuals at risk of functional decline. Because oral and physical frailty may influence each other bidirectionally, management should extend beyond screening to include appropriate oral care, nutritional support, physical exercise, and medical evaluation. Integrating simple oral frailty screening with objective systemic indicators may facilitate earlier identification of vulnerable individuals and strengthen medical–dental collaboration aimed at preventing frailty progression. Full article

Background: Sickle cell disease (SCD) and β-thalassemia are chronic thromboinflammatory disorders associated with venous, arterial, and microvascular thrombotic complications. However, evidence regarding disease-specific risk stratification and thrombosis prevention remains fragmented. This review summarizes current evidence on the mechanisms, risk identification, and prevention of thrombosis in these disorders. Methods: A narrative review of the literature was conducted using PubMed and Scopus to identify studies evaluating the thrombotic mechanisms, risk factors, biomarkers, and preventive strategies in SCD and β-thalassemia. Results: Thrombotic complications arise through interconnected mechanisms involving chronic hemolysis, nitric oxide depletion, endothelial dysfunction, phosphatidylserine exposure, microparticle generation, platelet activation, tissue factor expression, and enhanced thrombin generation. ADAMTS13–von Willebrand factor dysregulation may contribute to platelet adhesion and microvascular thrombosis, whereas NETosis and complement activation remain emerging mechanisms requiring further clinical validation. In SCD, thrombotic risk is associated with factors including pregnancy, recurrent hospitalization, central venous access devices, prior thrombosis, and pulmonary hypertension. In β-thalassemia, higher thrombotic event rates have been reported in non-transfusion-dependent disease, particularly among patients who have undergone splenectomy or have thrombocytosis, severe anemia, nucleated erythrocytosis, or pulmonary hypertension. Although several biomarkers reflect thromboinflammatory activity, none has been prospectively validated for routine risk prediction. Thromboprophylaxis is therefore generally limited to established high-risk clinical settings and is largely extrapolated from general venous thromboembolism guidelines. Observational data suggest that direct oral anticoagulants may be associated with similar rates of VTE recurrence and possibly lower rates of major bleeding than vitamin K antagonists in SCD; however, the certainty of evidence is very low. Conclusions: Current thrombosis management in SCD and β-thalassemia relies primarily on individualized risk assessment and extrapolation from general VTE recommendations. Prospective multicenter studies, randomized trials, and validated disease-specific risk prediction models are needed to optimize thrombosis prevention and anticoagulation strategies in these disorders. Full article

Background: Diabetes in males leads to hyperglycemia-induced oxidative stress and inflammation in the testis, resulting in apoptosis. Diabetes-induced testicular impairment has been linked to the implication with the gut–brain axis. Sodium butyrate, a product of the gut microbiota fermentation process, has been targeted for its anti-diabetic, anti-inflammatory, and antioxidative functions. This research, therefore, explored sodium butyrate as a therapeutic potential intervention in mitigating diabetes-induced testicular dysfunction. Methods: Thirty-five male rats were randomly assigned to five groups after diabetes was confirmed: healthy control (CON), sodium butyrate-treated (SBUT; 200 mg/kg orally), diabetic control (T1DM; 50 mg/kg STZ intraperitoneally), diabetes + sodium butyrate (T1DM + SBUT), and diabetes + insulin (T1DM + INSL, 0.9 I.U/100 g/day). Body weight, testicular weight, glucose homeostasis (fasting blood sugar, oral glucose tolerance, and glycated hemoglobin), lipid profile, testosterone level, sperm analysis, histopathology of the testis, and anti-apoptotic markers (B-cell lymphoma-2 (Bcl-2), Bcl-associated protein X (Bax), and Caspase-3) were all assessed. Results: Along with elevated blood glucose and glycated hemoglobin levels, diabetic rats showed a notable decrease in body weight, testicular mass, gonadosomatic index, sperm count, motility, viability, and normal morphology. Elevated Bax and Caspase-3 expression with reduced Bcl-2 were observed alongside testicular fibrosis, accumulation of collagen, and carbohydrate-rich substances. Sodium butyrate treatment, by downregulating Bax and Caspase-3 and upregulating Bcl-2, conserved testicular histoarchitecture, restored sperm quality, controlled apoptotic signaling, and markedly improved metabolic indices. Conclusions: Sodium butyrate displayed a protective role in the testis in diabetic conditions via the modulation of hyperglycemia-induced apoptosis, identifying this as a potential therapeutic intervention in diabetes-induced testicular dysfunction. Full article

Oral lichen planus (OLP) is a chronic, immune-mediated condition in which the oral epithelium acts simultaneously as a target of cytotoxic injury and a driver of persistent mucosal inflammation. This narrative review examines Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling as a network of cell- and cytokine-dependent signaling modules rather than a single linear pathway. Human OLP tissues show elevated expression of JAK1, phosphorylated JAK1, and various STAT-family proteins across both epithelial and inflammatory compartments. Functional modules demonstrate that IFN-γ–JAK1/JAK2–STAT1 sensitizes basal keratinocytes to cytotoxic attack, while JAK2/STAT3 regulates epithelial survival, tight-junction integrity, and E-cadherin/CD103-dependent intraepithelial lymphocyte retention. Additionally, metabolic and redox inputs converge on the STAT3–CCL5 axis to reinforce T-cell recruitment, with spatial analyses placing cytotoxic T cells directly at the epithelial interface. Although clinical responses to targeted JAK inhibitors (including JAK1, JAK1/2, JAK1/3, JAK3/TEC, and TYK2 agents) are encouraging, most current evidence remains observational. Because inhibitor selectivity is relative, therapeutic efficacy alone cannot identify the primary upstream cytokine driver. Advancing OLP management requires moving beyond broad pathway inhibition toward spatially resolved phospho-endotyping linked with standardized clinical phenotypes, mechanistic biomarkers, and targeted local therapies to enable a true precision treatment strategy. Full article

Background: Hemolytic jaundice, characterized by excessive bilirubin production and hepatic dysfunction, currently lacks effective therapeutic strategies targeting its underlying mechanisms. Methods: This study evaluated the therapeutic potential of the aqueous extract of Inonotus obliquus (IO) in ameliorating hemolytic jaundice through modulation of the gut–liver axis. A murine model of hemolytic jaundice was induced by phenylhydrazine (PHZ) administration, and IO was orally administered as the intervention. Antibiotic depletion and FMT verified gut microbiota dependence. Liver injury, serum bilirubin, gut microbiome, and metabolites were assessed. Results: IO treatment significantly alleviated PHZ-induced hemolytic jaundice in mice. Notably, antibiotic-mediated depletion of the gut microbiota abolished the hepatoprotective effects of IO, whereas fecal microbiota transplantation (FMT) from IO-treated donors conferred marked amelioration of hyperbilirubinemia in recipient mice. Integrative multi-omics analysis identified Limosilactobacillus reuteri and Lactobacillus johnsonii as the predominant microbial species altered by IO. Furthermore, IO upregulated the expression of farnesoid X receptor (FXR) and pregnane X receptor (PXR) in both hepatic and intestinal tissues and also increased the expression of bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2). These alterations were correlated with an increased excretion of bile acids and bilirubin into the intestinal lumen, thereby mitigating hepatic injury. This process may be associated with the modulation of gut microbiota. Conclusions: These findings collectively provide evidence of a significant correlation between IO treatment and the mitigation of hemolytic jaundice, achieved by modulating the enterohepatic circulation of bile acids and bilirubin through the regulation of gut microbiota. Our results highlight the potential of IO as a microbiota-directed nutritional strategy for the management of jaundice. Full article

Titanium dioxide nanoparticles (TiO₂-NPs) are widely used nanomaterials, but their potential systemic toxicity following chronic exposure remains a significant concern. This study investigated whether mitochondrial dysfunction represents a key mechanistic link between oxidative stress, apoptosis, and organ injury induced by TiO₂-NPs. Male Wistar rats were orally exposed for 90 days to TiO₂-NPs (15–31 nm) at doses of 215 or 500 mg/kg body weight. Mitochondrial analyses revealed significantly impaired respiratory activity, increased membrane permeability, and mitochondrial swelling, indicating disruption of mitochondrial function and electron transport chain integrity. These alterations were accompanied by increased reactive oxygen species production; depletion of antioxidant defenses, including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), and glutathione S-transferase (GST); and enhanced lipid peroxidation. Increased caspase-3 activation further suggested the involvement of mitochondria-dependent apoptotic pathways. Histopathological examination confirmed significant hepatorenal damage, including hepatocellular degeneration, inflammatory infiltration, vascular alterations, and glomerular and tubular lesions. Overall, integrating mitochondrial, oxidative, apoptotic, and histopathological findings supports a mechanistic model in which mitochondrial bioenergetic dysfunction acts as a central event linking oxidative imbalance to apoptosis and tissue injury. These findings contribute to a better understanding of TiO₂-NP-associated health risks and provide mechanistic insights relevant to the safer development and application of nanomaterials. Full article

Background/Objectives: To investigate laryngeal elevation velocity (LEV) as a candidate physiological marker of swallowing safety in post-radiotherapy dysphagia patients with cricopharyngeal muscle dysfunction (CPMD), we examined its association with airway safety and whether the LEV–upper esophageal sphincter (UES) opening relationship differed before versus after botulinum toxin injection, used here as a within-subject physiological perturbation. Methods: This retrospective cohort study included 18 post-radiotherapy patients with nasopharyngeal carcinoma (NPC) and CPMD who underwent botulinum toxin injection into the cricopharyngeal muscle (median total dose, 30 U; range, 20–40 U) and completed videofluoroscopic swallowing studies (VFSSs) before and after intervention. Primary outcomes were the Penetration–Aspiration Scale (PAS) and UES opening diameter; secondary outcomes included the Functional Oral Intake Scale (FOIS), laryngeal elevation (LE) and LEV. Associations were evaluated using generalized estimating equations (GEEs) with LEV × treatment interaction terms to assess whether they differed across pre- and post-injection states. Results: Following botulinum toxin injection, FOIS scores improved significantly (median, 4 to 5; p < 0.001), with concurrent increases in LEV (median, 149.86 to 201.12 C2–4%/s; p = 0.027) and UES diameter (median, 21.10 to 23.30 C2–4%; p = 0.039); PAS scores and laryngeal elevation displacement did not change significantly. Higher LEV was associated with lower odds of unsafe airway invasion (PAS 5–8) in univariate analysis (odds ratio per 100-unit increase, 0.38; 95% confidence interval [CI], 0.17–0.86; p = 0.021). A significant LEV × treatment interaction was observed for UES diameter (p = 0.021). Conclusions: In post-radiotherapy NPC patients with CPMD, higher LEV was associated with airway safety, and the LEV–UES relationship differed across pre- and post-injection states. Although the study design does not permit conclusions about treatment efficacy, LEV may represent a candidate load-sensitive marker of swallowing safety, warranting further investigation. Full article

Diabetic peripheral neuropathy (DPN) is a common and disabling complication of diabetes, but treatment still focuses largely on symptom control rather than modification of the underlying nerve injury. Mitochondrial dysfunction is increasingly implicated in the response of peripheral nerves to chronic hyperglycemia, although the literature is spread across different mitochondrial pathways, experimental models, biomarkers, and clinical settings. We therefore conducted a scoping review, following the Joanna Briggs Institute framework, to map this evidence and examine how far it has extended to oral and craniofacial neuropathic manifestations. PubMed, Scopus, and SpringerLink were searched using a predefined Population–Concept–Context strategy, and two reviewers independently screened records in Rayyan. Of 40,863 records identified, 853 studies met the eligibility criteria; 462 (54.2%) were published between 2021 and 2026. Most studies were preclinical. In the hierarchical evidence map, oxidative stress/redox imbalance was the largest evidence-mapping category (n = 591; 69.3%), followed by Schwann-cell degeneration (n = 147; 17.2%) and bioenergetic dysfunction (n = 77; 9.0%), whereas mitophagy (n = 14; 1.6%) and mitochondrial dynamics (n = 14; 1.6%) were much less frequently represented. Craniofacial neuropathy (n = 6; 0.7%) and oral neuropathy (n = 4; 0.5%) represented only a small proportion of the evidence map. Across these domains, recurrent pathways included Nrf2/Keap1 antioxidant defense, NF-κB-associated neuroinflammation, mitochondria-dependent apoptosis, and AMPK-SIRT-PGC-1α signaling. Clinical translation was limited, although mitochondrial DNA copy number, SOD3, and 8-hydroxy-2′-deoxyguanosine were reported as candidate biomarkers. Overall, the expanded evidence base confirms substantial growth in mitochondrial research in diabetic neuropathy but remains predominantly preclinical, with a particularly pronounced translational gap in oral and craniofacial neuropathy. Full article

Chronic low-grade inflammation (metaflammation) is a key contributor to obesity-associated metabolic disorders and their cardiovascular complications. This study investigated the effects of CXT29, a novel dual cyclooxygenase-2 (COX-2) inhibitor and thromboxane prostanoid receptor (TP) antagonist, in comparison with its parent compound etodolac, in a murine model of diet-induced metabolic dysfunction. Four-week-old male C57BL/6 mice were fed either a standard diet or a high-fat diet for 18 weeks and subsequently treated with etodolac (20 mg/kg/day) or CXT29 (25 mg/kg/day) by oral gavage for 5 weeks. High-fat-diet-fed mice developed increased body weight, impaired glucose tolerance, altered circulating metabolic hormones, liver dysfunction, steatosis, inflammatory cell infiltration, and systemic inflammation. Both treatments attenuated systemic inflammation and improved the metabolic alterations induced by the obesogenic diet. Notably, CXT29, but not etodolac, attenuated the increase in circulating plasminogen activator inhibitor-1 (PAI-1), a biomarker associated with cardiovascular risk. These findings indicate that pharmacological inhibition of COX-2 improves metabolic dysfunction associated with diet-induced obesity. Furthermore, the additional TP antagonism provided by CXT29 does not compromise the metabolic benefits associate with COX-2 inhibition, while displaying a distinct effect on circulating PAI-1, supporting further investigation of this dual-target approach in obesity-associated metabolic dysfunction. Full article

Cannabinoid signaling has attracted increasing interest in diabetes because the endocannabinoid system regulates energy balance, glucose and lipid metabolism, inflammation, and tissue homeostasis. However, its therapeutic relevance remains uncertain. This study combined scientometric mapping with a critical synthesis of mechanistic, pharmacokinetic, and clinical evidence on cannabinoids and diabetes published between 2004 and 2024. A structured search of the Web of Science Core Collection identified 459 original research articles, which were analyzed using Bibliometrix and complementary visualization tools. Scientific production increased markedly after 2016 and became progressively more diversified, with growing prominence of inflammation, oxidative stress, cannabis exposure-related themes, and broader mechanistic and population-level research questions. Mechanistic evidence strongly implicates excessive peripheral CB1 signaling in hepatic lipogenesis, adipose dysfunction, impaired insulin responsiveness, and related metabolic abnormalities, whereas CB2-mediated effects remain context-dependent. Cannabidiol is supported mainly by preclinical evidence of anti-inflammatory, antioxidant, and tissue-protective activity rather than consistent glucose-lowering effects. Clinical translation is further constrained by formulation-dependent oral exposure, extensive first-pass metabolism, food effects, broad tissue distribution, drug-interaction potential, and interindividual variability. Clinical evidence remains limited: brain-penetrant CB1 blockade improved selected metabolic outcomes but was restricted by psychiatric toxicity, while cannabidiol has not demonstrated consistent glycemic efficacy. Overall, cannabinoid research in diabetes shows substantial mechanistic development but limited clinical convergence. Future progress will require compound- and target-specific strategies, peripheral or tissue-selective modulation, standardized formulations, exposure–response characterization, appropriate patient stratification, and clinically meaningful outcome assessment. Full article

Background: Micronutrient imbalance is now recognized as a modifiable risk factor driving the progression of age-related hearing loss (ARHL). Zinc, an indispensable dietary trace nutrient, acts as a structural cofactor and transcriptional regulator of a broad panel of antioxidant enzymes to sustain systemic and cellular antioxidant defense capacity. Nevertheless, the therapeutic value of zinc nutritional supplementation and its precise molecular mechanisms against age-dependent cochlear degeneration remain largely uncharacterized. Methods: We established aging mouse models to observe the phenotypic changes caused by disrupted cochlear zinc nutritional homeostasis, and applied oral supplementation of bioavailable zinc glycinate to intervene in ARHL. In vitro D-galactose (D-gal) stimulation was adopted to induce cellular oxidative damage, followed by a series of mechanistic assays to detect the expression of core antioxidant molecules and determine mitochondrial function. Results: Disrupted cochlear zinc nutritional homeostasis induced progressive hearing loss and severe hair cell degeneration in aging mice. Conversely, oral zinc glycinate supplementation significantly relieved age-related hearing decline and reduced oxidative injury of cochlear hair cells. As a nutritional intervention, zinc glycinate significantly elevates the levels of key intracellular antioxidants (SOD, GSH, and GPX4) and rescues mitochondrial dysfunction induced by D-galactose triggered reactive oxygen species accumulation. Moreover, the protective effect of zinc glycinate may be associated with the upregulation of metal-responsive transcription factor 1 (MTF-1), which in turn suppresses the D-galactose-induced hyperactivation of the pro-inflammatory cGAS-STING pathway. Conclusions: Dietary zinc glycinate supplementation offers potential protection against cochlear aging. This auditory benefit may involve MTF-1 upregulation and inhibition of the cGAS-STING pathway. Collectively, these findings provide preclinical evidence supporting further investigation of zinc glycinate as a potential nutritional intervention for ARHL. Full article

Chronic kidney disease (CKD) appears linked to changes in the gut microbiota, intestinal barrier defects, and microbiota-driven changes in metabolite profiles. Experimental evidence links gut microbiota disturbances to kidney injury through pathways such as microbial metabolism, inflammation, immune signals, and epithelial barrier dysfunction. Still, applying this knowledge in clinical practice for patients with CKD remains difficult. For instance, one study on indoxyl sulfate and p-cresyl sulfate levels in a patient showed that, beyond being synthesized by the intestinal microbiota, the host can also metabolize or alter these metabolites. In addition, they undergo impaired renal clearance and can be secreted by the tubules. Moreover, most human microbiome-related studies are observational, making it difficult to determine the causal role of bacterial dysbiosis. Disease, dietary factors, medication, and other comorbid conditions are major confounders. Microbiota-directed means of altering the composition of the microbiota, such as changing diet, using prebiotics, probiotics, synbiotics, oral adsorbents, and even fecal microbiota transplantation, have, to varying degrees, affected the composition of the gut microbiota, levels of uremic toxins, short-chain fatty acids, and markers of inflammation. They have also been connected to leaky gut syndrome. However, evidence that these actions delay eGFR decline or prevent kidney failure, cardiovascular events, hospitalization, or mortality remains limited. Postbiotics and microbiota-derived metabolites in pure form are distinct experimental therapies and need to be assessed independently. This article reviews the gut kidney axis at different levels of evidence and distinguishes preclinical mechanisms, human associations, surrogate biomarker responses, and clinical outcomes. It points out why impressive mechanistic and biomarker results have not translated into better kidney or cardiovascular outcomes. Future research should use standardized methodologies, provide more detail on microbial functions and host metabolite metabolism, and test microbiome-targeted therapies in sufficiently powered randomized controlled trials with meaningful endpoints. Full article

Background/Objectives: Insulin resistance (IR) and metabolic Syndrome (MSy) have been linked to cognitive decline, but their presence in mild cognitive impairment (MCI) and Alzheimer disease (AD) remains unclear. We evaluated MSy and IR in nonobese, nondiabetic older adults with cognitive dysfunction. Methods: The cross-sectional study included 143 participants aged 65–90 years: 62 with AD, 41 with MCI, and 40 cognitively preserved controls. Anthropometric measures, blood pressure, fasting glucose, insulin, and lipid levels were assessed. Diabetes was excluded by oral glucose tolerance testing. IR was estimated using HOMA-IR, and MSy was diagnosed according to International Diabetes Federation (IDF) criteria. Group differences and associations with cognitive impairment were assessed using analysis of variance and regression analyses. Results: Fasting insulin increased from controls to MCI and AD (7.18 ± 4.32, 13.76 ± 6.89, and 18.58 ± 8.19 mU/L), as did HOMA-IR (1.49 ± 0.98, 3.35 ± 1.72, and 4.59 ± 2.19, p < 0.05). Compared with controls, both cognitively impaired groups had higher fasting glucose, TCh, LDL-ch and lower HDL-ch (all p < 0.05), whereas triglycerides did not differ (p = 0.266). MSy prevalence was 22.5% in controls, 46.3% in MCI, and 35.5% in AD; however, the overall difference was not statistically significant (p = 0.079). In binary logistic regression analysis, sex, age, LDL-ch, and HOMA-IR were independently associated with cognitive impairment (all p < 0.05). Conclusions: Increased IR was more consistently associated with cognitive impairment than the presence of MSy, with the highest degree of IR observed in AD. These findings support an association between metabolic dysfunction and cognitive impairment and suggest that IR may represent a potential target for preventive and therapeutic strategies. Full article

Background/Objectives: Metabolic syndrome (MetS) increases susceptibility to myocardial ischemia/reperfusion (I/R) injury through metabolic disturbance, hypertension, and oxidative stress. This study aimed to compare the effects of liraglutide and semaglutide on post-ischemic cardiac function, oxidative stress, and histomorphological changes in rats with MetS. Methods: MetS was induced in male Wistar rats by a high-fat diet followed by low-dose streptozotocin. After confirmation of MetS, animals were treated with saline, liraglutide, or semaglutide for 6 weeks. Blood pressure, glycemia, oral glucose tolerance, and lipid profile were assessed during the protocol. In vivo cardiac function was evaluated by echocardiography, whereas ex vivo I/R injury was induced using the Langendorff technique. Cardiodynamic parameters, coronary flow, oxidative stress markers, and histological changes in the heart, liver, and pancreas were analyzed. Results: Both liraglutide and semaglutide improved the cardiometabolic profile of MetS rats, with semaglutide showing a more evident effect on body weight control. In the Langendorff model, both treatments improved post-ischemic recovery of myocardial contractility and relaxation during reperfusion. Treated animals also showed a more favorable oxidative stress profile, particularly lower superoxide anion levels and enhanced antioxidant defense. Histologically, both agents attenuated myocardial hypertrophy and collagen deposition, improved hepatic architecture by reducing inflammatory changes, and preserved pancreatic structure with less lipid accumulation and tissue injury. Conclusions: Liraglutide and semaglutide exerted significant cardioprotective and tissue-protective effects in experimental MetS complicated by myocardial I/R injury. These findings support their potential in limiting post-ischemic cardiac dysfunction and multiorgan damage in metabolically compromised conditions. Full article